The proposed experiments are designed to elucidate the mechanisms whereby iodide and other related monovalent anions are actively transported across the basal and apical cell membranes of the thyroid gland and also the mechanisms by which this anion transport system is regulated by thyrotropin. Multiple approaches will be used to study these mechanisms. These involve compartmentation measurements of the thyroid, kinetic studies with radioactive tracers of iodide, bicarbonate, and chloride uptake into whole thyroid glands and into luminal fluid, histometric measurements of follicle, cell and luminal size, electrolyte and acid-base measurements, assay of the activities of various enzymes (carbonic anhydrase, and bicarbonate- and Mg-ATPase) postulated to be involved in the thyroidal anion transport system, and microelectrode studies with pH, K and Cl ionic-exchanger, and transmembrane-potential-measuring electrodes to assess the potentials across the apical and basal cell membranes, and the K and Cl activities and pH of cellular and luminal fluids of the thyroid. The four different species to be used are selected because their thyroids range from a high cellular to luminal volume ratio (mice and rats) to a very low ratio (guinea pigs and turtles), have different abilities to transport iodide, and the follicles vary in size from small to very large (greater than 250 micrometers). These experiments are designed to test the hypothesis that in addition to transport of iodide inward, the thyroid transports bicarbonate in the same direction, and chloride in the opposite direction, and that HCO3-ATPase and carbonic anhydrase are the transport enzymes involved. Thyrotropin is postulated to regulate iodide transport by an action on these enzymes.